Prediction of survival in diffuse large B cell lymphoma treated with chemotherapy plus Rituximab
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE10846 | GEO | 2008/11/28
SECONDARY ACCESSION(S): PRJNA107335
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression profiling of DLBCL patient samples was performed to investigate, whether molecular gene expression signatures retain their prognostic significance in patients treated with chemotherapy plus Rituximab. The lymphnode, germinal center signature and a new angiogenesis signature were combined to a final multivariate model which defined quartile groups among Rituximab-CHOP-treated patients with distinct 3-year overall survival rates. Experiment Overall Design: The retrospective study included 181 clinical samples from CHOP-treated patients and 233 clinical samples from Rituximab-CHOP-treated patients.
2008-12-05 | E-GEOD-10846 | biostudies-arrayexpress
Project description:We studied 498 de-novo adult DLBCL cases, which had been diagnosed between January 2002 and October 2009, as part of the International DLBCL Rituximab-CHOP Consortium Program Study We perform global gene expression profiling from formalin fixed paraffin embedded 498 DLBCL tissues RNA by SPIA mediated microarray detection and identified the distinct subgroups of the disease within DLBCL, known as germinal-center-B-cell-like (GCB), activated B-cell-like (ABC), and unclassified DLBCL (UC).
2012-08-01 | GSE31312 | GEO
Project description:We studied 498 de-novo adult DLBCL cases, which had been diagnosed between January 2002 and October 2009, as part of the International DLBCL Rituximab-CHOP Consortium Program Study We perform global gene expression profiling from formalin fixed paraffin embedded 498 DLBCL tissues RNA by SPIA mediated microarray detection and identified the distinct subgroups of the disease within DLBCL, known as germinal-center-B-cell-like (GCB), activated B-cell-like (ABC), and unclassified DLBCL (UC). RNA of 498 FFPET DLBCL patient samples were extracted, amplified using a novel RNA amplicfication method, Single Primer Isothermal Amplification (SPIA, NuGen Inc.), and hybridized to Affymetrix HG-U133 Plus 2.0 GeneChips. This dataset is the collaboration between The University of Texas at MD Anderson Cancer Center and Roche Molecular Systems, Inc.
2012-07-31 | E-GEOD-31312 | biostudies-arrayexpress
Project description:Objective: We performed whole-blood transcriptomic profiling for patients with rheumatoid arthritis (RA) who received rituximab (RTX). We aimed to identify a molecular signature that could predict the clinical response to RTX and transcriptomic changes after RTX therapy.
2015-01-01 | GSE54629 | GEO
Project description:Purpose: Despite recent advances in the treatment of patients with aggressive lymphomas, still a significant fraction of patients will succumb to their disease. Thus, novel therapeutic strategies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects. Experimental Design: Antibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in vitro and in vivo models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Results: Overall, three different sensitivity profiles to antibody monotherapy or combination treatment were observed in in vitro models: while 2/11 cell lines were primarily sensitive to tafasitamab and 2/11 were predominantly sensitive to rituximab treatment, the combination of tafasitamab and rituximab resulted in enhanced cell death in 7/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combinatorial approach of the two antibodies resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model. Conclusions: This study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to antibody mono treatment in models of aggressive B-cell lymphoma in vitro and in vivo. Translational Relevance: The immunochemotherapy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) remains the standard of care for newly diagnosed DLBCL patients. However, 30-40% of patients are refractory or relapse after initial response to the immunochemotherapy, indicating a high-unmet medical need for these patients. Tafasitamab and rituximab target the B-cell surface proteins CD19 and CD20, respectively, and both antibodies feature overlapping modes of action , namely direct cytotoxicity, ADCC and ADCP. In this study, we show that the combination of tafasitamab and rituximab had additive and synergistic efficacy both in vitro and in vivo. Our findings shed new light on the underlying mechanism of the combination of both antibodies and lay the ground to translate the results into improved outcome for patients with aggressive lymphoma in future clinical trials.
2023-10-22 | GSE211829 | GEO
Project description:Diffuse large B-cell lymphoma is an aggressive tumor, killing approximately 200,000 people each year. Rituximab, a recombinant monoclonal CD20 antibody, added to the treatment scheme in 1997 improved both progression-free survival and general survival rate. Despite the existing treatment and relatively high cure rate, 30-40% of the patients develop a relapse or are originally resistant. Long noncoding RNAs (lncRNAs) have been implicated as regulators of numerous important cancer-related processes, including establishment and maintenance of anti-cancer drug resistance. However, their role in DLBCL resistance to the treatment is poorly understood. In this study, we analyzed gene expression in DLBCL cell lines, either sensitive or resistant to rituximab.
2021-01-03 | GSE159852 | GEO
Project description:Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification sys-tem based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n _ 270; treated with rituximab plus CHOP [R-CHOP], n _ 869) gathered across geo-graphic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different co-horts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
2015-03-24 | GSE56313 | GEO
Project description:Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification sys-tem based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n _ 270; treated with rituximab plus CHOP [R-CHOP], n _ 869) gathered across geo-graphic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different co-horts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
2015-03-24 | GSE56314 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below: GSE56313 and GSE56314 Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification sys-tem based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n _ 270; treated with rituximab plus CHOP [R-CHOP], n _ 869) gathered across geo-graphic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different co-horts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
2015-03-24 | GSE56315 | GEO
Project description:Bendamustine plus rituximab (BR) therapy has demonstrated favorable clinical outcomes in the treatment of DLBCL patients who are intolerant to R-CHOP therapy. In vitro, BR therapy exhibits a synergistic cytotoxic effect on DLBCL cell lines. Mechanistically, BR induces pyroptosis in DLBCL cells by activating the cGAS-STING pathway, leading to the release of inflammatory factors and the formation of an "immunologically hot" microenvironment. Additionally, BR therapy upregulates MHC molecules on the tumor cell surface, thereby augmenting T cell activation and function.
2024-08-01 | GSE249466 | GEO